For more than a decade, umbilical cord blood (CB) has been investigated clinically as an alternative source of hematopoietic progenitors for allogeneic transplantation of patients lacking an HLA-matched marrow donor. Fewer T-cells and/or less developed T-cells in CB compared to marrow allows for the possibility that CB grafts will produce less Graft vs. Host Disease (GVHD), the major cause of morbidity and mortality in the allogeneic transplant setting. Other potential advantages include the ability to markedly increase the number of allografts available and thus the number of patients who could be transplanted, given the availability and ease of collecting CB from placental veins prior to disposal of the placenta, compared to collecting bone marrow or peripheral blood progenitor cells (PBPCs) from living donors. This new source of hematopoietic progenitors has allowed CB banks to target collection of units with human leukocyte antigen (HLA) types such as those of minority African American and Hispanic populations, which are under-represented in the National Marrow Donor Program Registry.
Since the first CB transplant performed in 1988, more than 5,000 patients world-wide have received related or unrelated CB transplants for a variety of malignant and non-malignant diseases. The majority of CB recipients have been children although adults are increasingly receiving CB transplants when an HLA− matched donor is not available. The progression-free survival rates reported thus far are comparable to results achieved following allogeneic bone marrow transplantation (Barker J N et al., (2001)). Moreover, there are many reports of what appears to be less GVHD than that associated with bone marrow transplants, despite the use of CB grafts with substantially more donor-recipient HLA disparity than that tolerated in recipients of marrow or PBPC allografts. The major disadvantage of CB is the low cell dose, which results in slower time to engraftment and higher rates of engraftment failure when compared to bone marrow transplantation (Kernan N A et al. (1993)). In studies of CB transplantation published by Kurtzberg (Kurtzberg J., (1996)), Gluckman (Gluckman et al., (1997)), Rubinstein (Rubinstein P., (1998)), Rizzieri (Rizzieri D A et al., (2001)), and Laughlin (Laughlin M J et al., (2001)) the median times to an absolute neutrophil count (ANC) of ≧0.5×109/L ranged from 22 to 34 days. Median times to a transfusion-independent platelet count ≧20×109/L varied from 56 to over 100 days, with engraftment failure rates of 12-18%. However, the engraftment failure rate for the adult patients (>18 years old and/or >45 Kg) in those series was substantially higher, ranging from 10-62%. It is these larger, adult patients, who might benefit the most from the ex vivo expansion of CB progenitor cells.
From the studies referenced above, there appears to be a threshold effect in the total nucleated cell (TNC) dose of unmanipulated CB infused and time to engraftment. In Gluckman's study, engraftment and survival were superior in patients who received ≧3.7×107 TNC/Kg. This large a cell dose is not generally available for patients weighing more than 45 kg. For adult patients, it appears that recipients of ≧1.0×107 TNC/Kg had more favorable engraftment than recipients of lower cell doses. Kurtzberg et al., reported a linear correlation between the number of CB nucleated cells infused and time to neutrophil engraftment (p<0.002) in the unrelated CB transplant setting. These data suggest that giving more CB cells may result in faster neutrophil engraftment.